ABSTRACT Age-related macular degeneration (AMD) is the most common cause of severe visual loss in the developed world, affecting more than 10 million people in the United States alone. Approximately 1 in 3 people over the age of 75 are affected to some degree. A significant fraction of this disease is genetic, with major genetic risk factors on chromosomes 1 and 10. In this study, we will take advantage of molecular genetics, state of the art computer-assisted image analysis, large patient populations, well characterized donor eye tissue, induced pluripotent stem cells and CRISPR based genome editing to determine the molecular basis of how variations in AMD loci increase risk of AMD. These studies will provide new insight into the pathophysiologic mechanisms of AMD that will be valuable for the development of more specific diagnostic methods and more effective therapies.